The hypotheses to be tested in this proposal are that the post-ischemic immune response contributes to brain injury and that brain injury can be reduced by appropriately modulating the immune response. Soon after the onset of ischemic stroke, lymphocytes infiltrate the brain and an immune response is triggered against brain antigens. Using an animal model of transient middle cerebral artery occlusion, we will define the nature of the post-ischemic immune response and explore ways to manipulate that response for therapeutic benefit. The specific aims of the project are: 1) to determine the time between ischemic stroke onset and development of a cellular immune response directed towards brain antigens, and to analyze that response, 2) to determine the nature and time course of lymphocyte infiltration into brain after stroke, and 3) to define the therapeutic potential of modulating the post-ischemic cellular immune response.